The objectives of the proposed research are to examine the possibilities that somatostatin, a hypothalamic peptide, serves a control function in the secretion of hormones from pituitary and extrapituitary endocrine organs. It is intended to determine if somatostatin is a) transported to peripheral endocrine organs via the circulation or alternatively b) is synthesized and released locally and serves a neurotransmitter function. If either of these two questions can be answered affirmatively, it is proposed to evaluate the possibility that somatostatin release can be correlated with physiologic signals modulating the secretion of growth hormone (G.H.), glucagon and insulin. In addition, the effects of the pharmacologic agents which perturb neurotransmitter function will be examined. The approach to these problems will be predicated upon the development of a specific and high affinity antiserum to somatostatin to enable quantification in extracellular fluids by radioimmunoassay or histochemical localization within tissues. Preliminary studies have indicated the availability of such an antiserum and detailed characterization of affinity, specificity and applicability to measurement of possible circulating somatostatin will be pursued. It is proposed to use rat, baboon and man as experimental models to evaluate the presence of somatostatin in the hypophyseal portal, peripheral circulation and cerebral spinal fluid. It will be ascertained whether or not peripheral levels are compatible with those achieved by somatostatin infusion which cause inhibitory effects on pancreatic hormonal release. Attempts will be made to correlate somatostatin levels with a number of physiologic states in which G.H., glucagon and insulin secretion is altered. The possibility that aberrant somatostatin release is present in metabolic disorders such as acromegaly, obesity and diabetes mellitus will be evaluated. The metabolic clearance rate and distribution space of somatostatin will also be determined and its localization and distribution in a variety of rat tissues will be examined by microdissection, extraction and immunofluorescent technique.